Smad proteins, the mammalian homologs of the Drosophila Mothers against dpp (Mad), have been implicated as downstream effectors of TGFb/BMP signaling. Smad1, Smad5, and Smad8 are effectors of BMP2 and BMP4 function while Smad2 and Smad3 are involved in TGF-b and activin-mediated growth modulation. Smad4 has been shown to mediate all of the above activities through interaction with various Smad family members. Smad6 and Smad7 regulate the response to activin/TGFb signaling by interfering with TGFb-mediated phosphorylation of other Smad family members.
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